AB0038 HINDLIMB SUSPENSION INDUCES KNEE MALALIGNMENTS WITH PATELLOFEMORAL OSTEOARTHRITIS IN GROWING RATS
Authors: J. Ozawa, A. Ikeda, M. Kanehara, A. Kaneguchi, H. Moriyama
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Patellofemoral instability is a common disease in pediatrics and patients with Down's syndrome. Reduced weight bearing during growth in the rat hindlimb suspension (HS) model leads to abnormal morphologies of distal femur, which are associated with patellofemoral instability[1]. However, no study has examined whether reduced weight bearing can induce knee joint instability. <h3>Objectives</h3> The aim of this study was to test whether hindlimb suspension in skeletally immature rats affects knee joint alignments and patellofemoral joint pathology. We hypothesized that reduced weight bearing results in knee malalignments such as externally translocation of patella and lateral tibial rotation. Furthermore, lateral patellar dislocation occurs with arthritic changes in the patellofemoral joint. <h3>Methods</h3> Four-week-old female rats were used in this study. In HS groups, rats were applied hindlimb suspension for up to 8 weeks using a tail suspension method. Age-matched untreated rats were used as controls. Knee joints (tibia-femur complex) were isolated and three-dimensional reconstructed images were obtained using X-ray computed tomography. Tibial tubercle-trochlear groove (TT-TG), patellar tilt angle, and bisect offset were measured as indexes of femorotibial or patellofemoral joint malalignment. Histological analysis was also performed to evaluate the osteoarthritic changes in the patellofemoral joints. In addition, gene expression profiles of medial patellofemoral ligament (MPFL), which plays as a stabilizer of the medial aspect of the patella, were analyzed with microarrays in both groups at week 4. <h3>Results</h3> Knee alignment data are shown in Table 1. At week 8, TT-TG, patella tilt angle, and bisect offset in HS group were larger than those in age-matched control, respectively (all P &lt; 0.05). These results indicated that tibial external rotation, patellar tilt outward, and external displacement of patella, respectively. In addition, lateral patellar dislocation appeared frequently after 8 weeks of HS (5/8 knee joint, Fisher's exact test, P &lt; 0.05). Articular cartilage in the trochlear grooves decreased or disappeared at 8 weeks of HS, especially in the dislocated patellofemoral joint. Modified Mankin's histological score supported these osteoarthritic changes. Synovial hypertrophy was observed at 4 weeks and progressed at 8 weeks of HS. The findings were supported by OARSI synovitis score. Microarray analysis of MPFL revealed that the gene expression of matrix metalloproteinase (MMP)-2, -3, enzymes of collagen degradation, were higher in HS than control (log2 ratio: 1.24 and 3.09, respectively), and tissue inhibitor of metalloproteinase (TIMP)-3, -4, MMPs inhibitor, were lower in HS than control (log2 ratio: -1.79 and -2.84, respectively). <h3>Conclusion</h3> Reduced joint loading during growth resulted in knee malalignments such as external rotation of tibia, lateral tilt, and translocation of patella. In addition, high incidence of lateral patellar dislocation with concomitant patellofemoral OA was found after HS for 8 weeks. Patellofemoral instability may be involved in dysfunction of MPFL via degradation of collagens. Values are mean ± standard deviation. Different letters indicate statistically differences among same groups. *: significant difference between two groups at the same time point. Note: Statistically significant values for two-way ANOVA are indicated in bold. Cont: age-matched control. HS: hindlimb suspension. <h3>Reference</h3> [1]Ozawa J, Kaneguchi A, Ezumi S, Maeno T, Iwazawa J, Minanimoto K, Ikeda A. Effects of hindlimb suspension on development of proximal and distal femur morphological abnormalities in growing rats. J Orthop Res. 2022 Apr 30. doi: 10.1002/jor.25352. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.